A Smart "Energy NanoLock" Selectively Blocks Oral Cancer Energy Metabolism through Synergistic Inhibition of Exogenous Nutrient Supply and Endogenous Energy Production

Bibliographische Detailangaben
Veröffentlicht in:	Advanced materials (Deerfield Beach, Fla.). - 1998. - 35(2023), 3 vom: 03. Jan., Seite e2207384
1. Verfasser:	Xu, Yurui (VerfasserIn)
Weitere Verfasser:	Zhang, Xiaomin, Zhou, Anwei, Cheng, Can, Chen, Kerong, Zhou, Xinyuan, Zhang, Gui, Ding, Likang, Wu, Xiaotong, Ge, Haixiong, Wu, Heming, Ning, Xinghai
Format:	Online-Aufsatz
Sprache:	English
Veröffentlicht:	2023
Zugriff auf das übergeordnete Werk:	Advanced materials (Deerfield Beach, Fla.)
Schlagworte:	Journal Article anti-angiogenesis dual responsive NanoLock metabolic therapy mitochondrial dysfunction oral cancer Gold 7440-57-5 Peptides

Beschreibung
Zusammenfassung:	© 2022 Wiley-VCH GmbH. The major challenge in oral cancer is the lack of state-of-the-art treatment modality that effectively cures cancer while preserving oral functions. Recent insights into tumor metabolic dependency provide a therapeutic opportunity for exploring optimal treatment approaches. Herein, a smart responsive "Energy NanoLock" is developed to improve cancer metabolic intervention by simultaneously inhibiting nutrient supply and energy production. NanoLock is a pomegranate-like nanocomplex of cyclicRGD-modified carboxymethyl chitosan (CyclicRC, pI = 6.7) encapsulating indocyanine green and apoptotic peptides functionalized gold nanoparticles (IK-AuNPs), which together form a dual pH- and photoresponsive therapeutic platform. NanoLock exhibits good stability under physiological conditions, but releases small-size CyclicRC and IK-AuNPs in response to the tumor acidic microenvironment, leading to deep tumor penetration. CyclicRC targets integrins to inhibit tumor angiogenesis, and consequently blocks tumor nutrient supply. Meanwhile, IK-AuNPs specifically induce apoptotic peptides and photothermally mediated mitochondrial collapse, and consequently inhibits endogenous energy production, thereby facilitating cell death. Importantly, in both xenograft and orthotopic oral cancer models, NanoLock selectively eliminates tumors with little cross-reactivity with normal tissues, especially oral functions, resulting in prolonged survival of mice. Therefore, NanoLock provides a novel metabolic therapy to exploit synergistic inhibition of exogenous nutrient supply and endogenous energy production, which potentially advances oral cancer treatment
Beschreibung:	Date Completed 23.01.2023 Date Revised 23.01.2023 published: Print-Electronic Citation Status MEDLINE
ISSN:	1521-4095
DOI:	10.1002/adma.202207384